Impact of follow-up time and analytical approaches to account for reverse causality on the association between physical activity and health outcomes in UK Biobank

Author:

Strain Tessa1ORCID,Wijndaele Katrien1,Sharp Stephen J1,Dempsey Paddy C12,Wareham Nick1,Brage Søren1ORCID

Affiliation:

1. MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK

2. Physical Activity & Behavioural Epidemiology Laboratories, Baker Heart and Diabetes Institute, Melbourne, Australia

Abstract

Abstract Background The advent of very large cohort studies (n > 500 000) has given rise to prospective analyses of health outcomes being undertaken after short (<4 years) follow-up periods. However, these studies are potentially at risk of reverse causality bias. We investigated differences in the associations between self-reported physical activity and all-cause and cardiovascular disease (CVD) mortality, and incident CVD, using different follow-up time cut-offs and methods to account for reverse causality bias. Methods Data were from n = 452 933 UK Biobank participants, aged 38–73 years at baseline. Median available follow-up time was 7 years (for all-cause and CVD mortality) and 6.1 years (for incident CVD). We additionally analysed associations at 1-, 2- and 4-year cut-offs after baseline. We fit up to four models: (1) adjusting for prevalent CVD and cancer, (2) excluding prevalent disease, (3) and (4) Model 2 excluding incident cases in the first 12 and 24 months, respectively. Results The strength of associations decreased as follow-up time cut-off increased. For all-cause mortality, Model 1 hazard ratios were 0.73 (0.69–0.78) after 1 year and 0.86 (0.84–0.87) after 7 years. Associations were weaker with increasing control for possible reverse causality. After 7-years follow-up, the hazard ratios were 0.86 (0.84–0.87) and 0.88 (0.86–0.90) for Models 1 and 4, respectively. Associations with CVD outcomes followed similar trends. Conclusions As analyses with longer follow-up times and increased control for reverse causality showed weaker associations, there are implications for the decision about when to analyse a cohort study with ongoing data collection, the interpretation of study results and their contribution to meta-analyses.

Funder

Medical Research Council

National Health and Medical Research Council of Australia

Publisher

Oxford University Press (OUP)

Subject

General Medicine,Epidemiology

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